Courses schedule

InfoChemie Mo. (Lundi) 11 to 13(original: 10-12)

Credits 4No. students 6+2

-Chemistry and life science …. 11+2(not there)-others (informatics …) 2 (info)+1 physics(?)

BioInfo Mo. (Lundi) 8 to 11(original: 8-10, 12-13)

Credits 3No. students 6

-Chemistry and life science …. 11+2(not there)-others (informatics …) 1 physics(?) –the same guy above

CHEMISTRY students

-InfoChimie (2+2 Lecture + Projects)-BioInfo (2+1 Lecture + Exercises)

Total credits: 7 (4+3)

OTHER students

-Lecture InfoChimie OR BioInfo

-Projects if InfoChemie any Project if BioInfo Bio-oriented Projects only (P.B1-

B4)-Exercises none

Total credits: 4

Organization of the courses

Projects InfoChimieB. Bio-oriented Projects B1-4

E. Electronic Structure Projects E1-3

P. Physical Chemistry Projects P1-3

I. Inorganic Chemistry Projects I1-2

B. Bio-oriented Projects

Background:• (η6-arene)Ru(pta)2+ compounds kill selectively cancer-cells (Prof Dyson).• ESI-MS shows loss of arene ligand upon binding to ssDNA.• Atomistic binding mode unknown!

Project:• Learn molecular modeling: Materials Studio, AMBER, Gaussian.• “Build” Ru(pta)2+-ssDNA-adducts in a virtual environment.• Modify/adapt existing force fields (charges, bond lengths, ….).• Equilibrate constraint DNA-adducts with implicit solvent.• Identify possible binding modes (A, G, T, C).• (Option: Update FF and run expicit solvent MD.)• (Option: QM/MM check for stability of adduct.)

Ru-anticancer compounds binding to ssDNA

Supervision: C. Gossens, I. Tavernelli

P. B1

Background• HCA is a Zn based enzyme that converts CO2 into bicarbonate.

• After the reaction occurs, the bicarbonate molecule has to leave the active site of the enzyme while a water molecule takes its position binding to the metal.

Biased random walk of HCO3 through the enzyme

Human Carbonic Anhydrase IISupervision: S.Giani, I. Tavernelli, R. Lins

P. B2

Project•Run a biased random walk of the bicarbonate to find the pathway connecting the active side with the surrounding.•Compute the free energy profile for the same process.

MethodClassical molecular dynamics and enhanced sampling techniques (thermodynamic integration).

Exploring RNA folding mechanisms with simulated annealing

Supervision: Pascal Baillod

The gaga rna tetraloop

RNA GNRA tetraloops

•Extremely common in biologically active RNAs.

•Promote proper folding of secondary and tertiary structures in lager RNAs.

References:

Fiona M. Jucker et al., J. Mol. Biol. (1996) 264, 968-980

Höbartner et al., J. Mol. Biol. (2003), 325, 421-431

P. B3-part1

Background

Project:

•Classical md simulations of hairpin RNAs.

•High temperature (simulated annealing) will allow to break watson-crick base pair networks, cooling will enable to reform different folded conformation h-bond networks.

•The simulation trajectories will help understanding existing experimental folding kinetics results. GM LM

ener

gy

Simulation time

Simulated annealing

Exploring RNA folding mechanisms with simulated annealing P. B3-part2

Binding Affinities of IAP Tetrapeptide Inhibitors

IAPs inhibit caspase activity and are widely expressed in cancer cells. They are likely to play a role in both disease progression and resistance to therapy.

A number of tetrapeptides inhibitors (SMAC analogs) and their dissociation constants are known.

k-1

k1

State-of-the-art Poisson-Boltzmann electrostatics methods will be used to calculate the binding affinitiy energies for the IAP and its tetrapeptide inhibitors as well as our newly proposed non-peptidic inhibitor

P. B4

Supervision:Roberto Lins

E. Electronic Structure Projects

•Flavodoxin: small electron transferases active in low-electron potential pathways;

•Cofactor: Flavin Mono Nucleotide;

•Three oxidation states: oxidized quinone/semiquinone/hydroquinone;

•Redox potential highly influenced by the protein environment and experimentally known;

Supervision: Michele Cascella

Ref: Bradley L. H. et al., Biochemistry, 40, 8686-8695 (2001)

Characterization of redox statesof Flavin Mononucleotide in Flavodoxins

P. E1-part 1

Characterization of redox statesof Flavin Mononucleotide in Flavodoxins

Project

Parametrization of FMN in its oxidation states,

Study of dynamical properties of Flavodoxin/FMN complex in water by means of Classical Molecular Dynamics.(programs used: Amber and GROMACS packages).

P. E1-part 2

Supervision: Michele Cascella

Excited state deactivation mechanism in DNA base pairs

MotivationThe excited state deactivation mechanism specific for hydrogen-bonded dimers may account for the photostability of the Watson-Crick base pairs in DNA.

Experimental results Femtosecond time-resolved mass spectroscopy reveals an excited-state lifetime of of ~65 ps for the near planar hydrogen-bonded dimer, which is significant shorter than the lifetime of the monomers.

MechanismConical intersections (CI) connect the locally excited ππ* state (LE) and the electronic ground state (GS) with a ππ* charge-transfer state (CT) that is strongly stabilized by the transfer of a proton.

Project Study this de-excitation mechanism using TDDFT (time-dependent density functional theory) calculation.-code: CPMD and TURBOMOLE.

Lit: T. Schultz et. al., SCIENCE, 306, 1765-8, 2004.

Supervision: Ivano Tavernelli

P. E2

Characterisation of a Conical Intersectionusing ab-initio Molecular Dynamics

MotivationConical intersections (CI) are a fundamental mechanism of radiation-less transition between adjacent potential energy surfaces (PES).

System-Test system: Formaldimine. CI between first singlet excited state and the ground state- Intramolecular charge transfer through CI in the excited state of 4-(Dimethyl)aminobenzonitrile (DMABN).

Project - Sample a set of ground state configurations according to the equilibrium Boltzmann distribution.- After excitation follow the relaxation of the Franck-Condon population along the excited PES until the conical intersection is encountered.- Construct a pair of reaction coordinates able to “resolve” the conical intersection and describe the topology of the PESs at the CI.

Tools TDDFT combined with ab initio MD (CPMD).

Supervision: Ivano Tavernelli and Mauricio Coutinho-Neto

P. E3

P. Physical Chemistry Projects

• Nanoscale devices of general interest in modern physics;

• Challenging objects for theoretical computations, as standard quantum chemical techniques either fail or are too expensive;

Supervision: Michele Cascella, Ivano Tavernelli

Ref: Cazzato et al.: J Chem. Phys. 120, 9071-9076 (2004).

P. P1-part 1 CO microsolvation in superfluid He droplets

Project Determination of the equilibrium geometries of the CO-Hen

clusters (n =1, 2,…6) by atom-centered vdW corrected pseudopotentials.

(Software: CPMD.)

Ref.: VonLilienfeld O.A. et al., PRL, 93, 153004-1 (2004)

CO microsolvation in superfluid He droplets

P. P1-part 2

Supervision: Michele Cascella, Ivano Tavernelli

Electronic structure of the organic conducting polymers

The project involves the study of the band structures of a number of π-conjugated organic polymers (polyanylines, polypyrolles, polyphenylvinylenes, etc.) using Gaussian periodic boundary conditions code and the ability of density functional theory to predict band gaps (of Fermi densities of states). It requires some (but not too much) knowledge on the basics of condensed matter physics. The 2000 Nobel prize was awarded for the important discoveries in this field.

P. P2-part 1

Supervision: Oleg Yazyev

P. P2-part 2 Electronic structure of the organic conducting polymers

EPR Parameters of Cu2+ Complexes

• EPR (Electron Paramagnetic Resonance Spectroscopy): is a powerful tool used to collect information about the environment of nuclei possessing electrons with unpaired spin

• Project: use [Cu(NH3)4(H2O)2]2+ as a model system to check the validity of commercial quantum chemistry programs (ADF, Gaussian) to compute EPR parameters

• Methods: CPMD, ADF, Gaussian, if time allows QM/MM, classical MD

P. P3Supervision: MariaCarola Colombo

I. Inorganic Chemistry Projects

Ab initio calculation of 99Tc NMR chemical shifts

in technetium coordination complexes related to radiopharmeceuticals

The compounds of 99m technetium isotope are used in medical imaging. The goal of the project is the systematic study of the performance of density functional theory methods and GTO basis sets for accurate prediction of 99Tc NMR chemical shifts for a number of technetium coordination compounds in different oxidation states and coordination envi-ronment. The study of an importance of relativistic effects on 99Tc NMR chemical shifts is also an inte-resting option.

P. I1-part 1

Supervision: Oleg Yazyev

99Mo

99mTc

99Tc

99Ru(Stable)

67 hr

hr

2.2 X 105 yr

P. I1-part 2 Ab initio calculation of 99Tc NMR chemical shifts

in technetium coordination complexes related to radiopharmeceuticals

Description of a fluxional process in an hexametallic cluster compound

Background• Intramolecular exchange studied experimentally and theoretically

for Ir2Rh2(CO)12 (collaboration Prof Roulet)• Publication chosen as “hot topic paper” in Dalton Trans. 2005• [Ir6(CO)14 I ]- : NMR shows similar exchange reaction

– concerted motion: 3 – 6 and 3’ – 6’ exchange of edge-bridging CO

– this results in exchange of 5 and 2 positions of CO

Project• Learn TS-search with QM-packages: ADF, Gaussian• Describe the full fluxional process (CO-ligand movement)

– Identify the ground-state (C2-symmetry)– Identify the TS

top view ofoctahedral

cluster

Supervision: C. Gossens

P. I2

P. I3Calculation of the chemical potential

of metal ions in solution;A comparative study

MotivationCalculation of chemical properties of molecules in solution is a challenging subject of modern quantum chemistry. Examples are: pKa, reactivity indices, reaction free energies, electrochemical potentials and others.

SystemMetal ions in solution (Cu+, Ag+, Ruthinate, …)

Project Compare the electrochemical half-reaction potential of ions in aqueous solution for the different setup:- Full ab-initio aqueous sample- QM/MM setup made of a quantum ion solvated in a explicit “classical” bath with counter ions. Validation of Marcus theory for electron transfer (ET) processes in solution.

Tools DFT based grand canonical approach: “numerical titration”.

Supervision: E. Tapavizca, I. Tavernelli